2019 Fiscal Year Final Research Report
Construction of ventricular tissue from human iPS cell-derived cardiomyocytes on vECM-nanographene composite substrate
| Project/Area Number |
17K01352
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Yamagata University |
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Principal Investigator |
Feng Zhonggang 山形大学, 大学院理工学研究科, 准教授 (10332545)
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| Co-Investigator(Kenkyū-buntansha) |
中村 孝夫 山形大学, 大学院医学系研究科, 教授 (00142654)
小沢田 正 山形大学, 大学院理工学研究科, 教授 (10143083)
梅津 光生 早稲田大学, 理工学術院, 教授 (90132927)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 特性調節複合培養基質 / ヒトiPS細胞心筋分化 / 心筋サブタイプ分化誘導 / 再生組織構築 / 中間モジュール法 / 電気・ひずみ刺激 / バイオリアクタ |
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| Outline of Final Research Achievements |
In this study, we pursued the strategy of integrating the cardiomyocyte differentiation, selection, and tissue construction into a continuous in-vivo simulation process. To this end, a vECM+nGraphene culture substrate was developed, which was based on ventricular extracellular matrix hydrogel and patterned stretchable nanographene electrodes were embedded in. The biochemical, biomechanical, and electrical properties of the substrate can be adjusted by means of crosslinker, concentration change. and application of strain and electrical stimuli. Cardiomyocyte differentiation was conducted on the substrate, and ventricular tissue was engineered by stacking intermediate modules, which were the construction blocks developed by the above strategy. It was confirmed that the hierarchical structure can be formed based on the substrate. The enhancement of the specific genetic expression and cellular orientation were also implicated.
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| Free Research Field |
生体医工学・生体材料学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、vECMgel＋nGraphene培養基質による心臓・血管系の多種細胞の系統的な同時分化誘導および組織発生を目指して、まず独創的な生化学・構造・電気特性が調整できるvECMgel+nGraphene基質を開発した。また、再生組織構築についての新たな方法論―中間モジュール法を提唱しiPS細胞からorganoid発生の新たな研究展開と相まって組織構造発生の本質をつきとめる斬新なストラテジーを実行した。これらの革新的な方法は全ての再生組織構築に利用できることを示唆され、ヒトiPS 細胞をセルソースとする心筋再生組織の構築による心筋症の治療と創薬モデルの開発に極めて有意義な成果を得た。
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